tbuckley/cabot-search huggingface dataset:
Combined 18F-FDG and 11C-acetate positron emission tomography/computed tomography in staging and treatment decision in patients with hepatocellular carcinoma: A cost-effectiveness analysis.
Authors: Sik-Kwan Chan, Wan Hang Keith Chiu, Ho Fun Victor Lee, Varut Vardhanabhuti, Tan To Cheung, Albert Chan, Stephen L. Chan, Pek-Lan Khong, Kelvin Kwok Chai Ng, Wai-Kay Seto, Feng-Ming Spring Kong, Chi Leung Chiang
Journal: Journal of Clinical Oncology (2022)

e16176 Background: Dual-tracer positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose and 11C-acetate is increasingly used in the management of hepatocellular carcinoma (HCC). However, considering the high cost of dual-tracer PET/CT, there is a need to assess its value by considering both the efficacy and cost. Methods: In this retrospective cohort study, 223 dual-tracer PET/CT scans were performed in 206 patients between 2014 and 2020 for tumor staging for radiologically or histologically confirmed HCC. New lesion detection rate, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and changes in treatment allocation based on dual-tracer PET/CT were evaluated. Validation was performed on a cohort of staging patients from another institution (n = 48). A cost-benefit analysis model was built for the incurred costs and the impact of dual-tracer PET/CT findings on treatment strategy over conventional imaging was studied. Results: Of the 223 patients that underwent dual-tracer PET/CT for staging, new lesions were detected in 33 (14.8%) patients, resulting in BCLC upstaging in 26 (11.6%) and treatment modification in 16 (7.2%) cases. The external staging cohort showed similar findings where dual-tracer PET/CT resulted in 12.5% (6/48) BCLC upstaging and 10.4% (5/48) treatment modifications (concordance-index: 0.85; 95% CI: 0.82-0.88). In subgroup analysis of 200 patients performed for pre-treatment metastatic screening, dual-tracer PET/CT detected extra-hepatic metastasis in 11, 10, and 16 patients, respectively, and led to treatment modifications in all of these patients. Sixteen locoregional therapies (8%) were avoided (8 resections, 3 transplantations, and 5 TACEs), with an estimated cost saving of US$161,665 (US$808 / patient) from the use of dual-tracer PET/CT. Sensitivity analyses suggested that dual-tracer PET/CT is consistently more cost-saving than conventional imaging, irrespective of the changes in the cost of imaging, procedures, and the duration of hospital stay (range: US$112,945-210,385). The cost of PET/CT had the greatest influence on the cost savings. Conclusions: Comparing to conventional imaging, dual-tracer PET/CT improves tumor staging, alters treatment allocation and is cost-saving in patients undergoing pre-treatment metastatic screening. Our results demonstrated that the use of dual-tracer PET/CT provides additional value and improves patient care.
Telomerase and myocardin co-expressing mesenchymal cells increase survival and induce cardiac and vascular markers in cardiac stromal cells undergoing simulated ischemia/reperfusion
Authors: R Madonna, SG Guarnieri, CK Kovacshazi, AG Gorbe, ZG Giricz, YJ Geng, MA Mariggio, PF Ferdinandy, RD De Caterina
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac stromal cells (CSCs) contain a pool of cells with supportive and paracrine functions. Various types of mesenchymal stromal cells (MSCs) can influence CSCs in the cardiac niche through their paracrine activity. Ischemia/reperfusion (I/R) leads to cell death and reduction of the paracrine activity of CSCs. The forced coexpression of telomerase reverse transcriptase (TERT) and myocardin (MYOCD), known to potentiate anti-apoptotic, pro-survival and pro-angiogenic activities of MSCs isolated from the adipose tissue (AT-MSCs), may increase CSC survival, favoring their paracrine activities. Aim To investigate the hypothesis that CSCs feature improved resistance to simulated I/R (SI/R) and increased commitment toward the cardiovascular lineage when preconditioned with conditioned media (CM) or extracellular vesicles (EV) released from AT-MSCs overexpressing TERT and MYOCD (T/M AT-MSCs). Methods and Results Murine CSCs were isolated with the cardiosphere (CSps) isolation technique. T/M AT-MSCs and their secretome improved spontaneous intracellular calcium changes (Figure 1) and ryanodine receptor expression in aged CSps. The cytoprotective effect of AT-MSCs was tested in CSCs subjected to SI/R. SI/R induced cell death as compared to normoxia (28±4 vs 10±3%, p=0.02). Pretreatment with CM (15±2, p=0.02) or with the EV-enriched fraction (10±1%, p=0.02) obtained from mock-transduced AT-MSCs in normoxia reduced cell death after SI/R. The effect was more prononunced with CM (7±1%, p=0.01) or the EV-enriched fraction (2±1%, p=0.01) obtained from T/M AT-MSCs subjected to SI/R. In parallel, we observed lower expression of the apoptosis marker cleaved caspase-3 and higher expression of cardiac and vascular markers eNOS, sarcomeric α-actinin and cardiac actin. Conclusions The T/M AT-MSCs secretome exerts a cytoprotective effect and promotes development of CSCs undergoing SI/R towards a cardiovascular phenotype.
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Authors: Joshua Spurrier, LaShae Nicholson, Xiaotian T. Fang, Austin J. Stoner, Takuya Toyonaga, Daniel Holden, Timothy R. Siegert, William Laird, Mary Alice Allnutt, Marius Chiasseu, A. Harrison Brody, Hideyuki Takahashi, Sarah Helena Nies, Azucena Pérez-Cañamás, Pragalath Sadasivam, Supum Lee, Songye Li, Le Zhang, Yiyun H. Huang, Richard E. Carson, Zhengxin Cai, Stephen M. Strittmatter
Journal: Science Translational Medicine (2022)

Microglia-mediated synaptic loss contributes to the development of cognitive impairments in Alzheimer's disease (AD). However, the basis for this immune-mediated attack on synapses remains to be elucidated. Treatment with the metabotropic glutamate receptor 5 (mGluR5) silent allosteric modulator (SAM), BMS-984923, prevents β-amyloid oligomer-induced aberrant synaptic signaling while preserving physiological glutamate response. Here, we show that oral BMS-984923 effectively occupies brain mGluR5 sites visualized by [18F]FPEB positron emission tomography (PET) at doses shown to be safe in rodents and nonhuman primates. In aged mouse models of AD (APPswe/PS1ΔE9 overexpressing transgenic and AppNL-G-F/hMapt double knock-in), SAM treatment fully restored synaptic density as measured by [18F]SynVesT-1 PET for SV2A and by histology, and the therapeutic benefit persisted after drug washout. Phospho-TAU accumulation in double knock-in mice was also reduced by SAM treatment. Single-nuclei transcriptomics demonstrated that SAM treatment in both models normalized expression patterns to a far greater extent in neurons than glia. Last, treatment prevented synaptic localization of the complement component C1Q and synaptic engulfment in AD mice. Thus, selective modulation of mGluR5 reversed neuronal gene expression changes to protect synapses from damage by microglial mediators in rodents.
Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis
Authors: Yong Xiang Gwee, Daryl Kai Ann Chia, Jimmy So, Wim Ceelen, Wei Peng Yong, Patrick Tan, Chin-Ann Johnny Ong, Raghav Sundar
Journal: Journal of Clinical Oncology (2022)

The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM). The biology of GCPM is unique and aggressive, leading to a dismal prognosis. These tumors tend to be resistant to traditional systemic therapy, and yet, this remains the current standard-of-care recommended by most international clinical guidelines. As this is an area of unmet clinical need, several translational studies and clinical trials have focused on addressing this specific disease state. Advances in genomic sequencing and molecular profiling have revealed several promising therapeutic targets and elucidated novel biology, particularly on the role of the surrounding tumor microenvironment in GCPM. Peritoneal-specific clinical trials are being designed with a combination of locoregional therapeutic strategies with systemic therapy. In this review, we summarize the new knowledge of cancer biology, advances in surgical techniques, and emergence of novel therapies as an integrated strategy emerges to address GCPM as a distinct clinical entity.
Long-term medical and functional outcomes of ependymoma survivors: A population-based, matched cohort study.
Authors: Hallie Coltin, Priscila Pequeno, Ning Liu, Derek S. Tsang, Michael D. Taylor, Eric Bouffet, Vijay Ramaswamy, Paul C. Nathan
Journal: Journal of Clinical Oncology (2022)

10054 Background: Ependymoma is the third most common pediatric central nervous system tumour. Treatment approaches are intensive and may include surgery, radiation, and chemotherapy. There are no longitudinal population-based cohort studies evaluating the long-term medical and functional outcomes of survivors of childhood ependymoma. Methods: Using a provincial pediatric cancer registry, all 5+ year ependymoma survivors diagnosed between 1987-2015 in Ontario, Canada were identified and matched to cancer-free population controls based on age, sex, and geographical location. Cases were followed from the index date (5 years from latest of diagnosis, or relapse/subsequent malignancy prior to age 18 years) until December 31, 2020 or censorship (death, or relapse/ new cancer after age 18 years). Clinical data were linked to administrative health databases to estimate the cumulative incidences and cause-specific hazard ratios (HR) of mortality, hospitalizations, strokes, hearing loss requiring a hearing aid, receipt of homecare services, and subsequent malignant neoplasms (SMNs) between cohorts, accounting for matching and competing risks. Results: Of 166 ependymoma diagnoses in the study period, 70 (42.2%) were excluded, most commonly due to early death prior to the index date. Ninety-six cases were matched to 480 controls (Table). The 10-year survival probability after the index date was 92.8% in cases and 99.6% in controls (HR 9.3, 95% CI 2.3-45.2, p=0.002). Compared to controls, cases were at higher risk of hospitalization (HR 3.2, 95% CI 2.2-4.6, p&lt;0.0001), stroke (HR 33.3, 95% CI 5.7-629.1, p&lt;0.0001), and receiving homecare services (HR 4.1, 95% CI 2.5-6.5, p&lt;0.0001). Cases were at high risk of hospitalizations, strokes, hearing loss, and SMNs, with cumulative incidences of 64.7% (95% CI 46.6-78.0), 9.7% (95% CI 3.4-19.9), 13.5% (95% CI 5.3-25.5), and 12.8% (95% CI 4.7-24.9) at 20-years post index date, respectively. Conclusions: As survival of pediatric ependymoma improves, establishing the burden of late morbidity is critical. Dedicated screening programs for late sensory and neurovascular sequelae are warranted, as are interventions during and following treatment to mitigate the risk of developing such complications. [Table: see text]
Gene expression profiling for breast cancer in the Philippines: Real-world data on feasibility, possible disparities, and clinical implications for LMICs.
Authors: Markyn Jared Ngo Kho, Mark Richard Kho
Journal: Journal of Clinical Oncology (2022)

e12569 Background: Racial, biological and socioeconomic disparities have most recently been shown to impact on specific molecular subtypes of breast tumors and on its clinical implications including the decision to omit adjuvant chemotherapy. Despite considerable logistical and cost constraints, we provide the first-ever documented and tangible profile of gene expression of breast cancers in the Philippines for a better understanding of its role in facilitating future testing and health policy making in an LMIC setting. Methods: This is a case series review of the 70-gene (MammaPrint) and 80-gene (BluePrint) signature done among Filipino patients from Dec 2013 to Nov 2021. Data on demographics, tumor characteristics, adjuvant therapy received and clinical risk assessment in the MINDACT study to c-low or c-high were gathered and analyzed. Results: Thirty-six females aged 36-75 years with invasive breast carcinoma Stage I to IIB had the following profile: Low Risk Luminal A (19, 52.8%), High Risk Luminal B (7, 19.4%), High Risk Her-2 (3, 8.3%), High Risk Basal (7, 19.4%). All low-risk patients underwent adjuvant endocrine therapy alone thus foregoing otherwise clinically recommended chemotherapy. No significant trend (in age, laterality, tumor grade and stage) can be discerned within all stratification groups except in the following areas: Histology: low risk profile in lobular carcinoma (n=2) Tumor Size: high risk profile in all tumors measuring 4.1 – 5 cms (n=4) Nodal Status: low risk profile in 6 of 8 patients with node+ disease LVI among node- patients: low risk profile in all 6 LVI+ tumors HR status: high risk profile in all 7 tumors with HR- status Her-2 neu status: good IHC test correlation with genomic subtype HR and Her-2 neu status: HR+her2- status in all 19 low risk tumors while high risk basal subtype in all 5 HR-her2- or triple-negative (TNBC) tumors Clinical risk in MINDACT: low genomic risk in 11 of 25 (44%) c-high patients. Conclusions: Gene profiling of breast cancer in a resource-limited setting is feasible and imperative to avoid chemotherapy and/or overtreatment. Clinically relevant disparities may exist which in turn can affect outcomes, decisions and health policies in adjuvant therapy and overall cancer care.[Table: see text]
The impact of classic Hodgkin lymphoma (cHL) on informal caregivers: Results from the cHL—Real-world observations from physicians, patients, and caregivers on the disease and its treatment (CONNECT) study.
Authors: Darcy R. Flora, Andrew M. Evens, Nicholas Liu, Kristina S. Yu, Rachel Byrd, Supriya Kumar, Michelle Fanale, Katie Holmes, Carlos Flores Avile, Andy Surinach, Susan K. Parsons
Journal: Journal of Clinical Oncology (2022)

e24004 Background: The health and work productivity burden informal cHL patient (pt) caregivers face is unknown. As part of the US-based CONNECT study, we evaluated caregivers’ burden and role in treatment (tx) decisions by relation to the pt: spouse/partner (SP) vs other (parent, child, friend, other relative). Methods: The CONNECT caregiver survey was an IRB-approved online survey administered from Dec 2020-Mar 2021 to self-identified current or former adult cHL pt caregivers. Health-related quality of life (HRQoL, PROMIS-Global), work impact (WPAI), decision-making, tx selection, and physician communication were assessed. Statistical significance was at the 95% confidence level. Results: 209 caregivers (58% women; median age 47 yrs; 54% employed; 53% SP) completed the survey. At completion, 69% cared for pts diagnosed in the past 1-2 yrs; 48% of pts cared for had stage III/IV cHL and 58% were in remission/not receiving active tx. While caregiver HRQoL was similar to that of the general population on the PROMIS-Global, employed caregivers had work impairment (29%) from caregiving activities (Table) which was higher when the pt was on vs off tx. Caregiving began at pt symptom onset for more SP vs other caregivers (61 vs 27%), and after the pt’s first tx for more other vs SP caregivers (34 vs 5%). 88% of caregivers discussed tx options with the pt. Cure, caregivers’ top tx goal (49%), was rated higher by SP vs other caregivers (56 vs 42%). Tx decisions with the pt (54 vs 23%) and tx option discussions with the doctor (52 vs 28%) were more common for SP vs other caregivers. More SP vs other caregivers had extensive tx option discussions with the pt (88 vs 68%), said it was important the doctor discussed managing side effects (94 vs 84%), felt the doctor provided adequate information about side effects (91 vs 71%), and felt aligned with the pt’s tx goals (93 vs 79%). Caregivers noted COVID-19 impacts like limiting daily activities to reduce COVID-19 risks (72%). Conclusions: Although cHL pt caregivers reported good HRQoL, caregiving impacted their work productivity regardless of relation to the pt. Cure was caregivers’ top tx goal. SP vs other caregivers were more involved and earlier, reporting alignment with pt tx goals and decision-making.[Table: see text]
Professional development in a Twitter hematology/oncology network for trainees.
Authors: Muhammad Salman Faisal, Andrea Anampa-Guzmán, Aakash Desai, Ghulam Rehman Mohyuddin, Ariela Lucy Marshall
Journal: Journal of Clinical Oncology (2022)

11034 Background: While resources exist to address the needs of graduate medical trainees, online resources to assist trainees with specialty-specific professional development have not been fully developed or described in the past. The Hem-Onc Fellows Network (@HemOncFellows) is an online community for hematology-oncology trainees in all stages of training, including medical students, residents, fellows, and doctoral students. The network's goals are to provide professional development in hematology-oncology, create a community and safe space for hematology-oncology trainees, and amplify the voices and needs of trainees. Methods: The @HemOncFellows Twitter account was created in February of 2021. The hashtag #HOFellows was registered and certified with healthcare Symplur. The network hosts Twitter Spaces (TS) with guests every two weeks and distributes a newsletter. Fifteen TS were held between July 2021 and February 2022. For each TS, a specific topic of professional development was discussed. At least one content expert was invited to each TS to provide additional commentary. Demographics of TS participants and newsletter subscribers were gathered and qualitative and quantitative analysis was performed. Results: Since its inception, the Hem-Onc Fellows Network has grown to more than 2200 followers. Symplur has over 500 #HOFellows tweets from November of 2021 to early February of 2022. The network organized 15 TS: 14 in professional development topics and one meet-and-greet for new matched fellows in December. TS had an average of 41 participants per event. Most participants were United States-based but there were participants from 21 countries worldwide. Forty-eight participants attended three or more spaces, including 15 hem-onc fellows and 17 internal medicine residents. The newsletter has 48 subscribers. Conclusions: We demonstrate that implementing a trainee network on Twitter attracted participation and engagement from a diverse pool of trainees worldwide. TS represents a novel educational tool for engaging trainees and facilitating professional development.
Trade-Offs Predicted by Metabolic Network Structure Give Rise to Evolutionary Specialization and Phenotypic Diversification
Authors: David M Ekkers, Sergio Tusso, Stefany Moreno-Gamez, Marina C Rillo, Oscar P Kuipers, G Sander van Doorn
Journal: Molecular Biology and Evolution (2022)

Abstract Mitigating trade-offs between different resource-utilization functions is key to an organism’s ecological and evolutionary success. These trade-offs often reflect metabolic constraints with a complex molecular underpinning; therefore, their consequences for evolutionary processes have remained elusive. Here, we investigate how metabolic architecture induces resource-utilization constraints and how these constraints, in turn, elicit evolutionary specialization and diversification. Guided by the metabolic network structure of the bacterium Lactococcus cremoris, we selected two carbon sources (fructose and galactose) with predicted coutilization constraints. By evolving L. cremoris on either fructose, galactose, or a mix of both sugars, we imposed selection favoring divergent metabolic specializations or coutilization of both resources, respectively. Phenotypic characterization revealed the evolution of either fructose or galactose specialists in the single-sugar treatments. In the mixed-sugar regime, we observed adaptive diversification: both specialists coexisted, and no generalist evolved. Divergence from the ancestral phenotype occurred at key pathway junctions in the central carbon metabolism. Fructose specialists evolved mutations in the fbp and pfk genes that appear to balance anabolic and catabolic carbon fluxes. Galactose specialists evolved increased expression of pgmA (the primary metabolic bottleneck of galactose metabolism) and silencing of ptnABCD (the main glucose transporter) and ldh (regulator/enzyme of downstream carbon metabolism). Overall, our study shows how metabolic network architecture and historical contingency serve to predict targets of selection and inform the functional interpretation of evolved mutations. The elucidation of the relationship between molecular constraints and phenotypic trade-offs contributes to an integrative understanding of evolutionary specialization and diversification.
Cost-related medication nonadherence and cost-saving strategies among Native Hawaiian and Pacific Islander cancer survivors.
Authors: Min Jee Lee, Eric Adjei Boakye, Ramzi Salloum
Journal: Journal of Clinical Oncology (2022)

e18531 Background: Although cost-related medication nonadherence resulting from sequelae of cancer and treatment has been reported in other racial/ethnic populations, little is known about cost-related medication nonadherence among Native Hawaiian and Pacific Islander cancer survivors. This study compared cost-related medication nonadherence among Native Hawaiian and Pacific Islander adults diagnosed with and without cancer and described the strategies cancer survivors used to offset the costs of medications. Methods: Using data from the 2014 Native Hawaiian and Pacific Islander National Health Interview Survey, we compared self-reported cost-related medication nonadherence, shifting spending from basic needs to afford medications, and cost reduction strategies among Native Hawaiian and Pacific Islanders diagnosed with and without cancer. Cancer survivors were those with a history of cancer (excluding nonmelanoma/unknown type of skin cancer). Descriptive statistics and logistic regression models were used to characterize (age, sex, sexual orientation, marital status, household income, educational attainment, health insurance status, comorbidities, self-rated health, activity limitation, and cancer type) and compare these populations. Results: Of 2,593 adults were included in the study, 151 (5.8%) reported a history of cancer, and 2,442 (94.2%) did not. Although 13.6% of cancer survivors and 7.7% without cancer reported cost-related medication nonadherence (p = 0.065), about 9.9% and 11.7% of those with and without cancer, respectively, reported delays in filling a prescription to save money. In addition, about 8.0% and 9.9% of those with and without cancer, respectively, reported taking less medication to save money. In weighted adjusted analyses, the rate of cost-related non-adherence among the two groups was similar, but with some subgroup differences noted by sex and household income. The use of cost reduction strategies was mostly similar among cancer survivors and those without cancer. Conclusions: Cost-related medication nonadherence is common among Native Hawaiian and Pacific Islanders, but appears at similar prevalence among those diagnosed with and without cancer.